This research is designed to study the prenatal transfer of antigen and its effects on the immune capabilities of the fetus using genetically inbred rats immunized with a synthetic polypeptide as the major experimental system. The specific objectives are: (1) to define the basic biological mechanisms responsible for the prenatal passage of antigen; (2) to delineate the role of prenatal passage of antigen, and its interplay with maternal antibody, in altering the immune responses of the fetus and in the pathogenesis of immunologically mediated diseases; and (3) to extend these findings to subhuman primates as the next step towards their applications to studies in humans. The rationale is based upon our previous experimental findings in inbred rats and upon an analysis of experimental and clinical observations in the literature. The transfer of antigen across the placenta will be explored in detail: the aggregated antigen is the only form capable of inducing prenatal sensitization of the fetus and it is transfered across the placenta, probably as a complex. Further studies will be done to eliminate cellular transfer as an important factor. The mechanism by which the antigen acts will be explored using a synthetic polypeptide antigen and the biologically complex antigens insulin, encephalogenic protein of brain and an oncogenic virus. The latter antigens will be used to explore the role of this phenomenon in inducing diseases important in humans which may have a significant immunological component, i.e. diabetes, demyelinating diseases of the CNS and cancer. The maternal-fetal system also provides a unique approach to studying the roles of antigen, antibody and antigen-antibody complexes in regulating the immune response. Studies in subhuman primates using tetanus toxoid will extend these finding to a species closer to man and will form the basis for later clinical work. The significance of these studies lies in the basic biological information that they will provide and the importance of this information for the development of useful therapeutic procedures employing "immunological engineering" in humans. A combination of amniocentesis for prenatal diagnosis and specific vaccination of the pregnant mother may provide a unique new approach in preventive medicine.